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Global RSV surveillance infers an 8%\u201327% mortality rate in preterm-born children, with 2.8 million\/year. Continuous surveillance studies, coupled with molecular epidemiological investigations, are essential to comprehend the virus\u2019s evolutionary dynamics and devise effective preventive strategies. The study investigates the evolutionary dynamics and molecular characterization of the RSV F-protein using bioinformatic pipelines on NCBI and GISAID data sets and molecular analysis of clinical specimens collected from children. We found S255N\/G, N262S, N268I, K272M\/N, and S275F\/A mutations in the heptad repeat region \u201cA\u201d that were associated with inducing resistance toward palivizumab from bioinformatics analysis of surveillance data sets. Molecular characterization of RSV F protein from clinical specimens found L45F mutations responsible for forming new clades, L172Q and S173L substitutions for suptavumab resistance, and N276S mutations for potentially impacting palivizumab resistance. Six N-glycosylation sites are found at 27, 70, 116, 120, 126, and 500 in all RSV strains. Purifying selection, maintaining fusion protein stability, was observed. Phylogenetic analysis reveals genetic variability, with RSV B showing higher diversity than RSV A, forming distinctive clades belonging to B.D (BA9) and A.D (ON1) strains of RSV B and A, respectively. The phylodynamics of RSV indicate a uniform increase in effective population size. Understanding the F protein\u2019s structure and dynamics is essential for elucidating the virus\u2019s pathogenic mechanisms and developing effective vaccines and antiviral therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Respiratory syncytial virus remains a major cause of severe respiratory disease in infants, the elderly, and immunocompromised populations worldwide. Despite recent advances in monoclonal antibodies and vaccines, the virus continues to evolve, posing challenges for long-term control. The RSV fusion (F) protein is central to viral entry and the primary target for neutralizing antibodies, yet little is known about its global evolutionary dynamics and drug-resistance associated changes. By integrating large-scale surveillance data with clinical isolates, our study identifies critical mutations, glycosylation patterns, and evolutionary pressures that shape the diversity of the F protein. These findings provide mechanistic insight into how RSV adapts under immune and therapeutic pressure, highlighting both vulnerabilities and conserved features of the F protein. Continuous monitoring of these evolutionary patterns will be crucial for maintaining vaccine effectiveness and informing the development of next-generation therapeutics to reduce RSV-associated morbidity and mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02983-25","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T13:00:18Z","timestamp":1777640418000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Phylodynamics and molecular epidemiology of the respiratory syncytial virus fusion protein in China"],"prefix":"10.1128","volume":"14","author":[{"given":"Muhammad Nabeel","family":"Amjad","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese 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